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Updated: Jul 30, 2025
Patient Derived Cell Culture and Isolation of CD133+ Putative Cancer Stem Cells from Melanoma
Published on: March 13, 2013
FGF-trapping hampers cancer stem-like cells in uveal melanoma
Alessandra Loda1, Stefano Calza1, Arianna Giacomini1
1Department of Molecular and Translational Medicine, University of Brescia, viale Europa 11, 25123, Brescia, Italy.
Background:
Cancer stem-like cells (CSCs) are a subpopulation of tumor cells responsible for tumor initiation, metastasis, chemoresistance, and relapse. Recently, CSCs have been identified in Uveal Melanoma (UM), which represents the most common primary tumor of the eye. UM is highly resistant to systemic chemotherapy and effective therapies aimed at improving overall survival of patients are eagerly required.
Methods:
Herein, taking advantage from a pan Fibroblast Growth Factor (FGF)-trap molecule, we singled out and analyzed a UM-CSC subset with marked stem-like properties. A hierarchical clustering of gene expression data publicly available on The Cancer Genome Atlas (TCGA) was performed to identify patients' clusters.
Results:
By disrupting the FGF/FGF receptor (FGFR)-mediated signaling, we unmasked an FGF-sensitive UM population characterized by increased expression of numerous stemness-related transcription factors, enhanced aldehyde dehydrogenase (ALDH) activity, and tumor-sphere formation capacity. Moreover, FGF inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor graft assay, resulting in the reduction of tumor growth. At clinical level, hierarchical clustering of TCGA gene expression data revealed a strong correlation between FGFs/FGFRs and stemness-related genes, allowing the identification of three distinct clusters characterized by different clinical outcomes.
Conclusions:
Our findings support the evidence that the FGF/FGFR axis represents a master regulator of cancer stemness in primary UM tumors and point to anti-FGF treatments as a novel therapeutic strategy to hit the CSC component in UM.
Insights
Targeting the Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) pathway may offer a novel therapeutic strategy for Uveal Melanoma (UM). This approach can effectively target cancer stem-like cells (CSCs) responsible for tumor initiation and resistance.
Area of Science:
- Oncology
- Ophthalmology
- Molecular Biology
Background:
- Cancer stem-like cells (CSCs) drive tumor initiation, metastasis, and treatment resistance in various cancers.
- Uveal Melanoma (UM), the most common primary eye tumor, exhibits high resistance to systemic chemotherapy.
- Effective therapies are urgently needed to improve patient survival in UM.
Purpose of the Study:
- To identify and analyze a subset of UM CSCs with stem-like properties.
- To investigate the role of the Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) signaling pathway in UM stemness.
- To explore the therapeutic potential of targeting the FGF/FGFR axis in UM.
Main Methods:
- Utilized a pan Fibroblast Growth Factor (FGF)-trap molecule to isolate and study UM CSCs.
- Performed hierarchical clustering on The Cancer Genome Atlas (TCGA) gene expression data to identify patient clusters.
- Assessed stemness markers, aldehyde dehydrogenase (ALDH) activity, and tumor-sphere formation capacity.
Main Results:
- Disruption of FGF/FGFR signaling identified an FGF-sensitive UM population with enhanced stemness markers and ALDH activity.
- FGF inhibition reduced UM CSC survival and tumor growth in vivo (chorioallantoic membrane assay).
- Hierarchical clustering of TCGA data revealed correlations between FGFs/FGFRs and stemness genes, defining three distinct clinical outcome clusters.
Conclusions:
- The FGF/FGFR axis is a key regulator of cancer stemness in primary UM.
- Targeting the FGF/FGFR pathway represents a promising novel therapeutic strategy against UM CSCs.
- Anti-FGF treatments could effectively target the CSC component in Uveal Melanoma.
